Pharmacologic treatment of repetitive behaviors in autism spectrum disorders: evidence of publication bias

Pediatrics. 2012 May;129(5):e1301-10. doi: 10.1542/peds.2011-3285. Epub 2012 Apr 23.

Abstract

Objective: The goal of this study was to examine the efficacy of serotonin receptor inhibitors (SRIs) for the treatment of repetitive behaviors in autism spectrum disorders (ASD).

Methods: Two reviewers searched PubMed and Clinicaltrials.gov for randomized, double-blind, placebo-controlled trials evaluating the efficacy of SRIs for repetitive behaviors in ASD. Our primary outcome was mean improvement in ratings scales of repetitive behavior. Publication bias was assessed by using a funnel plot, the Egger's test, and a meta-regression of sample size and effect size.

Results: Our search identified 5 published and 5 unpublished but completed trials eligible for meta-analysis. Meta-analysis of 5 published and 1 unpublished trial (which provided data) demonstrated a small but significant effect of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.22 [95% confidence interval: 0.07-0.37], z score = 2.87, P < .005). There was significant evidence of publication bias in all analyses. When Duval and Tweedie's trim and fill method was used to adjust for the effect of publication bias, there was no longer a significant benefit of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.12 [95% confidence interval: -0.02 to 0.27]). Secondary analyses demonstrated no significant effect of type of medication, patient age, method of analysis, trial design, or trial duration on reported SRI efficacy.

Conclusions: Meta-analysis of the published literature suggests a small but significant effect of SRI in the treatment of repetitive behaviors in ASD. This effect may be attributable to selective publication of trial results. Without timely, transparent, and complete disclosure of trial results, it remains difficult to determine the efficacy of available medications.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Child
  • Child Development Disorders, Pervasive / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Publication Bias*
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Stereotyped Behavior / drug effects*
  • Stereotypic Movement Disorder / drug therapy*

Substances

  • Antidepressive Agents
  • Serotonin Uptake Inhibitors